Imaging Brain, Neurocognitive and Pubertal Maturation During Adolescence

描述（由申请人提供）：最近在理解儿童期和青春期人类大脑中发生的与年龄相关的结构成熟变化方面取得了巨大进展，但大脑结构的可变性非常大，即使在相同实足年龄的个体之间也是如此。文献表明，控制情感、情绪、编码信息的边缘结构的发育失调，可能先于提供冲动和风险评估调节控制的执行中心（额叶皮质）发育。神经发育、神经内分泌、行为和环境因素可能与大脑结构和功能的变化以及青春期认知能力的巨大变化有关，但我们对这些因素几乎一无所知。在这个项目中，我们计划以2年的扫描间隔对120名9 - 15岁的典型发育青少年进行纵向研究，并收集脑成像（结构MRI、弥散张量成像和功能MRI，包括反应抑制、奖励加工、延迟折扣、面部情感加工）、神经认知（强调执行功能和认知控制）、生理性成熟（使用Tanners分期）和激素(皮质醇、睾酮，雌激素和脱氢表雄酮（DHEA）数据（使用唾液样本）以及日常压力测量。利用这些丰富的多模态成像、行为、认知和激素数据，我们将解决以下具体目标：1)区分青春期激素依赖与非激素依赖的神经发育效应；2)评估脑变化与认知（认知控制、执行功能、日常压力）和动机（如奖励敏感性）等行为指标之间的关系；3)评估脑变化与青春期发展指标之间关系的性别差异。据我们所知，这将是第一个通过使用尖端的功能和结构MRI综合多模态图像分析来纵向检查青少年大脑发育的研究，并将激素与其他与年龄相关的环境和行为相关因素区分开来。

DESCRIPTION (provided by applicant): Enormous progress has been made recently in understanding the age-related structural maturational changes that occur in the human brain during childhood and adolescence, but variability in brain structure is very large, even among individuals of the same chronological age. The literature suggests an offset in development of limbic structures which control affect, emotion, encoding information, which may develop prior to the executive centers (frontal cortices) that provide regulatory control over impulses and risk assessment. Almost nothing is yet known about neurodevelopmental, neuroendocrine, behavioral and environmental factors that likely relate to variability in brain structure and function, and cognitive abilities that change so dramatically during adolescence. In this project, we propose to longitudinally study 120 typically developing adolescents between 9 and 15 years of age with 2-year scan intervals, and to collect brain imaging (structural MRI, diffusion tensor imaging and functional MRI with tasks of response inhibition, reward processing, delayed discounting, facial affect processing), neurocognitive (with emphasis on executive functioning and cognitive control), physical sexual maturation (using Tanners staging), and hormonal (cortisol, testosterone, estrogen and Dehydroepiandrosterone (DHEA) using saliva samples) data as well as measures of daily stress. With these rich multimodal imaging, behavioral, cognitive and hormonal data, we will address the following specific aims: 1) to distinguish hormone-dependent from non-hormone dependent neurodevelopmental effects in adolescence, 2) to evaluate relationships between brain changes and behavioral indices of cognition (cognitive control, executive functions, daily stress) and motivation (e.g., reward sensitivity), and 3) to evaluate gender differences in relationships between brain changes and indices of pubertal progression. To our knowledge, this will be the first study to undertake such challenges by using cutting-edge integrative multimodal image analyses of functional and structural MRI to examine, longitudinally, brain development in adolescents and to distinguish hormonal from other age-related environmental and behavioral correlates. PUBLIC HEALTH RELEVANCE: The proposed research to study adolescent brain development using integrated multimodal neuroimaging, neurocognitive, stress, and hormonal measures longitudinally in typically developing children and adolescents is of the utmost importance. The beginning of adolescence is a time of dramatic physical, emotional and social change, and is also associated with the onset of psychopathology such as depression, suicide, and substance abuse. To provide a framework for understanding how risks during adolescence can tip the balance toward pathological outcomes in youth and adulthood, models of typical brain development need to evaluate interactions between hormonal and physical sexual maturity and the still-maturing neural systems responsible for social interactions, affective states and cognitive control.